The invention relates to a method of applying a mixture of at least two liquid components to form a biomaterial at a desired site and is more particularly concerned with the application of at least two components which will form surgical sealant, e.g., a fibrin sealant.
Numerous biomaterials, e.g., biopolymers, are utilized in the medical arena. Many of these are formed from the combination of two or more liquid components and can therefore be formed in situ by the co-application of such components. An example of this is a surgical sealant, e.g., a fibrin sealant, which can be formed by the co-application of a fibrinogen component and a thrombin component.
U.S. Pat. No. 4,359,049 to Redl discloses a double barrel syringe for applying a tissue adhesive such as fibrin glue or fibrin sealant to a human or animal in need thereof. The fibrin sealant described comprises predominantly two major components, a fibrinogen-containing component and a thrombin-containing component, each in liquid form upon use. Essentially, the thrombin and fibrinogen, when mixed, provide that the peptide chains of the fibrinogen are cleaved and conditions are provided so that the resulting fibrin polymerizes into a clot which is useful for sealing fluid and air leaks, in haemostasis and to connect tissue. To avoid premature clot formation double-barreled applicators are employed which, of course, keep the two components separate until application to a patient is required. The ""049 patent discloses that pistons within the two cartridges, each containing one component, can be commonly actuated to dispense fluid simultaneously from each.
Other prior art patents describe various mixing methods for mixing two or more components used in these and other surgical sealants. For example, U.S. Pat. No. 5,116,315 assigned to Hemaedics describes a mixing head where the liquid conduits leading from the component cartridge enter a mixing chamber fashioned so as to provide a swirling of the components before they exit via a common exit channel. Adequate mixing of the components is desired so as to form a uniform fibrin sealant. Inefficient mixing results in the co-administration of fibrinogen and thrombin which may only result in a small yield of actual sealant. A difficulty with fibrin sealant applicators can be the premature formation of the clot within the device, especially those devices where the components are mixed within a mixing head and/or those devices wherein the components exit through a common channel. After the first spray of sealant is complete, a clot may block the exit channels rendering the applicator useless and greatly reducing the surgeon""s flexibility in carrying out the sealant part of the surgical procedure.
U.S. Pat. No. 4,631,055 to Immuno includes a gas conveying channel for blowing a gas through the needle or mixing head during discharge of the components. However, an even, uniform distribution of the materials over the anatomical area of interest is still not achieved. Indeed, a significant amount of the components are wasted.
U.S. Pat. No. 5,605,541 discloses a device and a method of applying components of a fibrin sealant. The device comprises a source of a gas and a reservoir for each component wherein the gas source and each of said components are discharged through separate apertures. Preferably, the gas is discharged through the center aperture and the fibrin sealant forming components are discharged separately through each of the annular apertures.
European Patent 592,242 to Edwardson et al. discloses the first completely autologous fibrin sealant. It provides for the co-administration of a fibrin monomer solution with a buffer solution which provides for the polymerization of the fibrin monomer and can be prepared in less than 30 minutes from a single source of blood (preferably that of the patient to receive the sealant). This breakthrough technology provides a fixed amount of fibrin monomer solution from a sample of about 140 to 160 ml of blood. Uniform and efficient mixing is even more important in order to benefit from this safe, efficient, autologous sealant product and therefore new devices and methods for applying two or more components to form a surgical sealant are required.
Ideal application of fibrin sealants involves an efficient utilization of the sealant components to maximize coverage and effective use. Efficient utilization is accomplished by, inter alia, sufficient mixing of the components, uniformly controlled application of the components, the ability to apply the components intermittently and minimization of aerosols. It is also desirable for the surgeon to be able to vary the application rates according to the particular procedure and to be able to work in close proximity, i.e., less than 10 cm and even less than 5 cm, away from the tissue to be sprayed.
Among the parameters which can be most devastating to the performance of sealant applicators are mixing and clogging. Insufficient mixing results in the co-application of individual sealant components and only a portion of the amount of sealant desired is actually formed. This results in waste and poor sealant performance. Because the sealant components begin or continue the coagulation cycle upon mixing with each other there are limitations to the Hemaedics device described above and most current sealant applicators are designed to mix the components outside of the device to avoid clogging. Those skilled in the art can appreciate that proper mixing and application are difficult to control given that the important mixing of components occurs as they leave the device rather than inside the device. The characteristics of the applied sealant film are greatly impacted by the mixing/spray parameters and the fluid dynamics of the two liquids as they exit the device tip or nozzle. Clogging is often the result of the premature contact of the sealant components within the device, however, the handling and transfer of blood within plastic and/or glass tubing and appliances, generally, is inherently problematic, especially as inner device/tubing dimensions become smaller.
U.S. Pat. No. 5,582,596 to Fukunaga et al. discloses a spray applicator suitable for fibrin sealants which can be connected to a gas supply. Two liquid nozzles are located concentrically within two larger gas nozzles. The ""596 patent states that the liquid nozzles protrude from the gas nozzle by from about 100 microns to 10 mm. The ""596 patent also states that the liquid nozzles are from about 1.0 mm to about 20 mm apart. A commercially available applicator for Bolheal(copyright) sealant which appears to be an embodiment of the ""596 patent actually has two liquid nozzles which protrude about 600 microns from the gas jets and which have inner diameters of about 625 microns wherein the liquid nozzles are on 3.0 mm centers or are about 2.4 mm apart. The product and ""596 patent suggest that low pressures, e.g. 0.75 kg/cm2 to 4.0 kg/cm2 can be used but no mention is made of airflow, or sealant flow rates. Spray angles, aerosols and working distances for this device still leave room for improvement.
WO 97/20585 discloses a novel spray applicator for fibrin sealants which utilizes xe2x80x9cin-linexe2x80x9d apertures in the spray tip for expelling air (or other gas) and sealant components. That system uses relatively low air flow, i.e., 1.25 liters/min with sealant rates of nearly 2.0 ml/min to nearly 5.0 ml/min. The apertures in the spray tip are only about 300 microns in inner diameter and about 200 microns apart, i.e., on 5 micron centers. It is believed that this device is among the smallest in nozzle dimensions for blood, i.e., fibrin sealant application. Aerosols are considerably reduced and spray angles and mixing improved, but a finer controlled spray with even less aerosols and more efficient utilization of sealant components would be a useful addition to the art.
In accordance with the present invention it has been found that enhanced mixing and application of two liquid components to form a biomaterial with minimized aerosols is achieved using air flow rates below about 1.25 liters/minute in combination with a ratio of air flow to total liquid flow of from about 150:1 up to about 1500:1. Preferably the air flow is below about 1 liter/ minute and the ratio of air flow to total liquid flow is from about 200:1 to about 1200:1. The parameters are ideally suited for the spray application of components which form a surgical sealant, e.g., a fibrin sealant. Also a part of the present invention are novel application methods for biomaterial, e.g., surgical sealant, components at liquid flows below 1.9 ml/minute, novel methods involving the mixing of such components on the exit surface of a spray tip or nozzle, novel spray tips and biomaterial applicators and methods for making such applicators.